Narrow Results

It is important for maintenance and understanding of health to make inquiries into the biological defence mechanisms. Yonezawa et al. came across an induction of yet unknown defence mechanisms in mice which acquired two types of radioresistance (decrease in bone-marrow death rate after midlethal exposure): one occured 2 weeks after preirradiation with 0.3–0.5 Gy and the other 2 months after 0.05–0.10 Gy of X-rays. To elucidate the acquired radioresistance induced after preirradiation with 0.5 Gy (in a shorter time case). recovery of blood cell counts after sublethal irradiation were measured in mice of ICR strain. Contrary to the common knowledge on radiation protection. recovery of blood cell counts of thrombocytes. leukocytes and erythrocytes after sublethal irradiation were not stimulated by the preirradiation. This study was planned to find some keys to elucidate the mechanism for the acquired radioresistance. Eleven elements. Cl. K. Ca. Cr. Mn. Fe. Ni. Cu. Zn. Se and Br. were analysed clearly in mice sera by PIXE.

Yonezawa et al. found an induction of yet unknown defence mechanisms(s) in mice which acquired radioresistance two weeks after small dose X-irradiation of 50 cGy. This study here was planned to find some keys to elucidate mechanism of the acquired radioresistance. Metal ions are well known to be important for enzyme activities as well as for metabolisms. Elements from Na to S were analyzed in identical mice sera used previously for the analysis of other heavier eleven elements. The analysis shows that decreases in P and S concentrations on 10 days after the 2nd irradiation of 5.0 Gy are prevented together with potassium reported previously. Contrary, on the 15th day, P and S decrease much compared with the control.

Pre-irradiation with 0.3-0.5 Gy of X-rays induces radioresistance (decreased bone marrow death) in ICR and C57BL strains of mice 2 weeks afterward. Recovery of blood cell counts of thrombocytes, leukocytes and erythrocytes was enhanced by the pre-irradiation. And the radio-resistance is acquired even in splenectomized C57BL mice. Elements in the bone marrow 11 days after the challenging dose of 5.0 Gy was determined by a PIXE analysis in three groups of mice: intact (with no irradiations), without pre-irradiation (control) and pre-irradiation (experimental) groups. Challenging irradiation decreased Mg, P, S, K, Ca and Zn levels, and the pre-irradiation enhanced the recovery of those levels, i.e. stimulated metabolism in bone marrow of irradiated mice. Increase in Fe in both control and experimental groups would indicate stimulated hemoglobin synthesis after challenging irradiation.

Radiotherapy plays a crucial role in the multimodal treatment of breast cancer. However, radioresistance poses a significant challenge to its effectiveness, hindering successful cancer therapy. Emerging evidence indicates that Nrf2 and HIF-1$\alpha$ are critical regulators of cellular anti-oxidant responses and that their overexpression significantly promotes radioresistance. Wogonin (WG), the primary component isolated from Scutellaria baicalensis, exhibits potential antitumor and reversal of multidrug resistance activities. Nevertheless, the role of WG in radioresistance remains unclear. This study aims to explore the effects of WG on the radioresistance of breast cancer. Our results indicate that Nrf2 and HIF-1$\alpha$ overexpression was observed in breast cancer tissues and was correlated with the histological grading of the disease. Radiation further increased the levels of Nrf2 and HIF-1$\alpha$ in breast cancer cells. However, WG demonstrated the ability to induce cell apoptosis and reverse radioresistance by inhibiting the Nrf2/HIF-1$\alpha$ pathway. These effects were also confirmed in xenograft mice models. Mechanistically, WG enhanced the level of the Nrf2 inhibitor Keap1 through reducing CpG methylation in the promoter region of the Keap1 gene. Consequently, the Nrf2/HIF-1$\alpha$ pathway, along with the Nrf2- and HIF-1$\alpha$-dependent protective responses, were suppressed. Taken together, our findings demonstrate that WG can epigenetically regulate the Keap1 gene, inhibit the Nrf2/HIF-1$\alpha$ pathway, induce apoptosis in breast cancer cells, and diminish acquired radioresistance. This study offers potential strategies to overcome the limitations of current radiotherapy for breast cancer.